Relapse to drug abuse is the single greatest problem in addiction treatment. Experimental evidence in humans and animals suggests that females are more prone to relapse than males, identifying a need for sex-specific treatment strategies for drug abuse. Aerobic exercise has emerged as an effective behavioral treatment for addiction, and studies suggest that it might be more effective to decrease drug abuse in females than males. The long-term goal of this project is to characterize exercise as a treatment for addiction in both males and females. The current aims are to examine the effects of aerobic exercise in male and female rats on relapse after a prolonged abstinence from drug use; determine whether exercise will reduce relapse-related neuroadaptations in brain areas important for addiction; and investigate differential effects of exercise in females vs. males. It is hypothesized that exercise will diminish relapse after prolonged abstinence, reverse or eliminate brain adaptations associated with prolonged abstinence, and act more effectively in females than in males. The experiments are designed to test the effects of voluntary wheel running in rats that are in prolonged withdrawal from intravenous cocaine self-administration, and the training potential of this project is to provide instruction in cellular and molecular experimental techniques paired with behavioral paradigms. To this end, behavioral measures, protein analysis, and neuronal morphology will be assessed. The proposed experiments have the potential to elucidate a novel sex-specific treatment for relapse and will give insight into the neurobiological mechanism of its action.